X-151396858-G-T

Variant names:

• chrX-151396858-G-T
• rs176451
• NM_001363810.1:c.19G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001363810.1(VMA21):​c.19G>T​(p.Gly7Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/12 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 21)
• Consequence: VMA21 NM_001363810.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.736

Genes affected

VMA21 (HGNC:22082): (vacuolar ATPase assembly factor VMA21) This gene encodes a chaperone for assembly of lysosomal vacuolar ATPase.[provided by RefSeq, Jul 2012]

ENSG00000287918 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08636907).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VMA21	NM_001363810.1	c.19G>T	p.Gly7Cys	missense_variant	Exon 1 of 3		NP_001350739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VMA21	ENST00000370361.5	c.19G>T	p.Gly7Cys	missense_variant	Exon 2 of 4	5		ENSP00000359386.1
ENSG00000287918	ENST00000660681.2	n.280C>A		non_coding_transcript_exon_variant	Exon 1 of 2
ENSG00000287918	ENST00000664935.1	n.161C>A		non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.53
DANN	Benign	0.94
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.1	T
PROVEAN	Benign	0.37	N
REVEL	Benign	0.075
Sift	Pathogenic	0.0	D
Vest4		0.089
MutPred		0.096		Loss of phosphorylation at S4 (P = 0.1161);
MVP		0.18
ClinPred		0.58	D
GERP RS		-2.6
gMVP		0.087

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs176451; hg19: chrX-150565330;